The Role of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapies in Early-Stage Breast Cancer: Current Practices, Treatment De-escalation, and Future Prospects.

Human epidermal growth factor receptor 2 (HER2)-targeted therapy has transformed the treatment paradigm for early-stage HER2-positive breast cancer, providing personalized and effective interventions. This comprehensive review delves into the current state of HER2-targeted therapies, emphasizing pivotal clinical trials that have demonstrated their substantial impact on long-term outcomes. Combination therapies that integrate HER2-targeted agents with chemotherapy exhibit enhanced tumor responses, particularly in neoadjuvant settings. Neoadjuvant chemotherapy (NACT) is explored for its role in tumor downsizing, facilitating breast-conserving surgery (BCS), and incorporating oncoplastic solutions to address both oncologic efficacy and aesthetic outcomes. Innovative axillary management post-NACT, such as targeted axillary dissection (TAD), is discussed for minimizing morbidity. The review further explores the delicate balance between maximal therapy and de-escalation, reflecting recent trends in treatment approaches. The therapeutic landscape of HER2-low breast cancer is examined, highlighting considerations in HER2-positive breast cancer with BReast CAncer gene (BRCA) mutations. Emerging immunotherapeutic strategies, encompassing immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy, are discussed in the context of their potential integration into treatment paradigms. In conclusion, the evolving landscape of HER2-positive early-stage breast cancer treatment, characterized by targeted therapies and multidisciplinary approaches, underscores the need for ongoing research and collaborative efforts. The aim is to refine treatment strategies and enhance patient outcomes in this dynamic and rapidly evolving field.

Information literacy in the digital age: information sources, evaluation strategies, and perceived teaching competences of pre-service teachers.

Introduction: Information literacy has become indispensable in navigating today's fast-paced media environment, with teachers playing a pivotal role in fostering reflective and critical digital citizenship. Positioned as future gatekeepers, pre-service teachers are the key to teaching media skills and especially information literacy to future generations of pupils. Given the particular challenges facing educators today compared to previous generations, it is important to determine whether the next generation of teachers feel adequately prepared and perceive themselves as competent to pass on these skills to their future pupils. However, previous research has highlighted deficiencies in formal learning opportunities at universities, underscoring the need for further investigation into pre-service teachers' information acquisition, evaluation practices as well as their perceived relevance to teaching, and person-related factors associated with their perceived competence in teaching information literacy. Method: An online questionnaire was presented to participants, employing a mixed-method approach. We qualitatively examined the sources of information used by pre-service teachers and the evaluation strategies they employ, while quantitatively analyzing relationships between pre-service teachers' person-related factors and their perceived teaching competence. Participants assessed their perceived teaching competence, perceived learning opportunities, self-efficacy (general and related to information assessment), perceived informedness, selective exposure, need for cognition, need for cognitive closure, and mistrust in media coverage. Results: Data from 371 participants revealed digital media dominance in information acquisition over traditional sources, albeit with a prevalence of surface-level evaluation strategies over reflective approaches. Two distinct dimensions of perceived competence in teaching information literacy emerged: one focusing on information assessment while the other centers on the understanding of news creation processes. Perceived competence in teaching information literacy was significantly associated with self-efficacy in information assessment, perceived informedness, selective exposure to information as well as perceived learning opportunities focusing on information evaluation. Moreover, pre-service teachers employing diverse information evaluation strategies demonstrated a heightened sense of perceived competence in teaching information assessment. Discussion: Our results provide valuable insights into the multifaceted nature of pre-service teachers' perceived competence in teaching information literacy. Theoretical implications for future research as well as practical implications for teacher education and the structure of future curricula are discussed.

Helicobacter pylori and Gastrointestinal Cancers: Recent Advances and Controversies.

Helicobacter pylori (H pylori), a gastric bacterium, has been extensively studied for its association with gastritis, peptic ulcers, and gastric cancer. However, recent evidence suggests its potential implications beyond the stomach, linking it to other gastrointestinal malignancies, such as esophageal cancer, liver cancer, pancreatic cancer, gallbladder cancer, and colorectal cancer. In light of the expanding research landscape and the increasing interest in exploring H pylori broader role in gastrointestinal tumorigenesis, this comprehensive review aims to elucidate the relationship between H pylori and gastrointestinal tumors. This review encompasses recent epidemiological studies, research progress, and emerging perspectives, providing a comprehensive assessment of the relationship between H pylori and gastrointestinal tumors. The findings highlight the captivating world of H pylori and its intricate involvement in gastrointestinal malignancies.

Integration of ELT strategies in science classrooms: Asian university teachers and students' perspectives.

This study investigated the integration of ELT (English language teaching) strategies in Asian university science classrooms. Guided by the exploratory-descriptive qualitative research as methodological framework, this investigation sought to answer the following research questions: (a) What are the perceptions of the science teachers in employing ELT strategies in science university classrooms? (b) What challenges and issues do science teachers see in the integration of the ELT strategies in university science classrooms? (c) What are the perceptions of the student participants on the roles of ELT strategies in science classrooms? This study used interviews with selected teachers and students as participants, and a lesson implementation. The analysis surfaces that both teachers and students have favorable opinions on the contributions of ELT strategies in science classrooms. The results of this study support the use of these strategies to foster effective communication and improve comprehension in science classrooms. While positive perceptions were evident, a few issues, however, surfaced: issues involving comprehension, written structure and spelling, and a lack of speaking skills among the students. These findings suggest the importance of addressing these specific areas for improvement through targeted instruction and practice. The implications of this study are also discussed.

Resilience among organ donation coordinators: a Canadian mixed-methods study.

Background: Organ and Tissue Donation Coordinators (OTDCs) are key to the success of deceased organ donation processes. However, reduced resilience can leave them susceptible to the incidence of work-related issues and decrease the quality of the care provided. Therefore, this study aimed to examine the extent of resilience and influencing aspects among OTDCs in Canada. Methods: Mixed-method (QUAN-qual) explanatory sequential design. Quantitative data was collected using an online cross-sectional survey approach with demographic data and the validated scales and analyzed using descriptive and inferential statistics. Qualitative data was collected using a descriptive approach with a semi-structured interview guide and analyzed using content analysis. Results: One hundred twenty participants responded to the survey, and 39 participants were interviewed. Most participants from the survey were female (82%), registered nurses (97%) and on average 42 years old. The quantitative data revealed that OTDCs had a high level of perceived compassion satisfaction (ProQOL-CS = 36.3) but a resilience score (CD-RISC = 28.5) lower than other groups of healthcare professionals. OTDCs with over a year of experience in the role were more likely to have higher levels of resilience. The qualitative data identified that participants saw resilience as crucial for their work-related well-being. Although coping strategies were identified as a key factor that enhance resilience, many OTDCs reported difficulty in developing healthy coping strategies, and that the use of unhealthy mechanisms (e.g., alcohol and smoking) can result in negative physical consequences (e.g., weight gain) and reduced resilience levels. Conclusion: Participants reported using a series of coping and protective strategies to help build resilience, but also difficulty in developing healthy mechanisms. The lack of healthy coping strategies were seen as contributing to negative work-related issues (e.g., burnout). Our findings are being used to develop tailored interventions to improve resilience and healthy coping strategies among organ donor coordinators in Canada.

Where the children play: Gender gaps in recess physical activity by age and playground area.

Objective: Recess contributes meaningfully to physical activity (PA), but recess time has declined. The study's purpose was to report PA by age, gender, and playground feature to inform potential playground configurations more conducive to PA during recess. Methods: Using the System for Observing Play and Leisure Activity in the Youth, kindergarten through 5th grade recesses were observed on at least four days at four schools in Little Rock, Arkansas, United States during May 2023. Target playground features were ball courts, grass, pavement, play structures, and swings. To provide inferential analysis, a comparison of conditional means across playground features, age, and gender was conducted using linear regression with robust standard errors clustered by school. Results: 3,356 playground scans (intercoder correlation = 0.93) were collected and aggregated by school, day, gender, age (grade), and target feature for a sample size of 292 observations. The gender gap was widest among 4-5th graders, 79 % (95 % CI: 72, 86) for males and 64 % (95 % CI: 58, 70) for females. Among females, PA was highest on swings [82 % (95 % CI: 77, 86)] and lowest on paved areas [56 % (95 % CI: 43, 69)]. Among males, it was highest on both swings [81 % (95 % CI: 75, 86)] and ball courts [83 % (95 % CI: 77, 89)] and lowest on grassy areas [64 % (95 % CI: 60, 67)]. Conclusion: Swings, courts, and play structures were associated with a higher proportion of children being engaged in PA. Research is needed to identify whether physical improvements to facilitate access to these features increase PA.

Elucidating the role of FOS in modulating the immune microenvironment through fibroblast and myeloid cell regulation in locoregional recurrent HNSCC.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) presents a significant clinical challenge, particularly due to its high propensity for locoregional recurrence. Current research underscores the need to unravel the complex interactions within the tumor microenvironment. This study addresses the critical gap in understanding how FOS modulates the immune landscape in HNSCC, with a focus on its influence on fibroblast and myeloid cell dynamics. METHODS: Employing a comprehensive approach, we analyzed tissue samples from HNSCC patients and adjacent non-cancerous tissues using bulk RNA sequencing complemented by in-depth bioinformatics analyses, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and immune infiltration assessment. A pivotal aspect of our research involved dissecting single-cell RNA-seq data from GSE234933 to elucidate the cell-type-specific expression of FOS. RESULTS: We found that FOS expression varies significantly in different cell populations in the HNSCC tumor microenvironment, especially in fibroblasts and myeloid cells. This expression difference may reflect the different roles of these cells in tumor progression and their impact on the tumor microenvironment. CONCLUSION: Our results uncover a significant correlation between FOS expression and key immune and hypoxia-related pathways, suggesting its integral role in the tumor microenvironment. These findings not only enhance our understanding of HNSCC pathogenesis but also highlight FOS as a potential therapeutic target. This study marks a significant step towards addressing the urgent need for targeted interventions in HNSCC, particularly in the context of locoregional recurrence.

Examining and mitigating racism in nursing using the socio-ecological model.

Racism in nursing is multifaceted, ranging from internalized racism and interpersonal racism to institutional and systemic (or structural) elements that perpetuate inequities in the nursing profession. Employing the socio-ecological model, this study dissects the underlying challenges across various levels and proposes targeted mitigation strategies to foster an inclusive and equitable environment for nursing education. It advances clear, context-specific mitigation strategies to cultivate inclusivity and equity within nursing education. Effectively addressing racism within this context necessitates a tailored, multistakeholder approach, impacting nursing students, faculty, administration, professional organizations, and licensing and accrediting bodies. This all-encompassing strategy recognizes that the interplay of interpersonal dynamics, community culture, institutional policies, and broader societal structures intricately shapes individual experiences. Nurses, nurse leaders, educators, organizations, and policymakers can work together to create a more equitable and inclusive nursing profession by targeting each of these levels. This transformational process can yield positive outcomes across various environments where nurses learn, work, and serve people and enable the demographic composition of nurses to better match the populations served.

Nomogram to predict central lymph node metastasis in papillary thyroid carcinoma.

Central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) is common. In our study, we built a nomogram to predict CLNM. We retrospectively analyzed 1,392 PTC patients. This group of patients was divided into a training cohort (including 1,009 patients) and a validation cohort (including 383 patients). Analyses of the correlation between inflammatory indicators, ultrasonic characteristics, pathological characteristics and CLNM were conducted. In the training cohort and validation cohort, the metastatic rates of CLNM were 60.16% and 64.23%, respectively. Univariate and multivariate logistic regression analyses demonstrated that Hashimoto's thyroiditis (HT), calcification, multifocality, capsule invasion, PLR (platelet-lymphocyte ratio) ≤ 130.34, large tumors and middle and lower positions were independent risk factors for CLNM. Then, we constructed a nomogram. The nomogram had good discrimination regardless of whether there was CLNM, with a C-index of 0.809. The calibration curve indicated that the nomogram had good visual and quantitative consistency (p = 0.213). Decision curve analysis showed that the nomogram improved the net clinical benefit with a threshold probability of 0-82% in the training cohort and 0-71% in the validation cohort. We constructed a nomogram to predict CLNM in PTC and assist surgeons in making personalized clinical decisions for PTC.

Implementing Lifestyle Medicine in Undergraduate Medical Education at Riphah International University, Pakistan.

The Need of the LM content in Medical undergraduate curriculum was imperative based on the mortality and morbidity statistics in Pakistan along with lack of LM training and unhealthy lifestyle of physicians themselves. Aims and Objectives for integrating LM content were designed including cognitive, affective and psychomotor domains of learning. while embedding LM content in an integrated modular system, every step was technically monitored and matched with the academic year, teaching methodology and importance of the topic. LM content was integrated in every educational activity from first to final year by adding or modifying LM learning objectives. The alignment of learning domains was in accordance with the teaching and assessment strategies. Teaching methods chosen were according to the designed learning objectives and phase of curriculum. LM content was assessed in formative and summative assessment through, single best and case cluster MCQs, reflections, OSPE. LM curriculum was communicated to teaching faculty and medical students through academic calendar, module guides and timetables. It was shared on Moodle and Teams. Educational environment incorporated both physical and virtual learning and has been supportive of lifestyle practices among medical students. The entire process of embedding LM content in medical education has been multifaceted. Different committees were formed including Steering, Core, implementation, and Evaluation Committees. Students were part of each committee. This write-up describes the evidence-based approach used to embed LM content in Undergraduate Medical Education and offers guidance to other undergraduate medical colleges that may wish to implement lifestyle medicine content.

A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides.

Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.

Tongue edema as an adverse drug reaction to low-dose olanzapine in a cancer patient receiving palliative care.

OBJECTIVES: Olanzapine is an atypical neuroleptic indicated for treatment of various psychiatric disorders, but it has also several indications in palliative care (PC) patients: opioids misuse, nausea not related to chemotherapy, anorexia-cachexia syndrome, and sleep and mood disorders. Peripheral and facial edema are a rare side effect of the treatment with olanzapine. I report a case of an advanced cancer patient cared receiving PC who developed moderate tongue edema on day 1 of a low dose of olanzapine. METHODS: A patient with advance and metastatic colon cancer presented moderate tongue edema on day 1 of a low dose (2.5 mg) of olanzapine for the treatment of his nausea, anorexia-cachexia syndrome, and mood disorder (mainly anxiety). RESULTS: The patient discontinued the drug with resolution of the edema. The day after he called our outpatients' service, a prompt physical examination, together with blood tests, excluded other differential diagnosis. SIGNIFICANCE OF RESULTS: To the best of our knowledge, this is the second case reporting head and neck localized edema due to olanzapine treatment in a patient with advanced cancer receiving PC. Considering the increasing use of olanzapine as off-label treatment in these patients (often for cluster symptoms), our report could help clinicians in daily practice and researchers on put a deeper focus on indications for olanzapine in PC.

Repeated sexual intercourse as a coping strategy for men with premature ejaculation.

BACKGROUND: Patients with premature ejaculation (PE) are often concerned and distressed about their sexual performance. Hence, they may be more willing to exploit their refractory period to employ sexual coping strategies in order to improve their unsatisfactory sexual intercourse compared with patients without PE. AIM: The study sought to verify the sexual coping strategies of patients with PE in the daily sexual activities. METHODS: We included both patients with PE and individuals without PE and analyzed their sexual behaviors and attitudes by means of detailed interviews and questionnaires. OUTCOMES: The main outcomes were perceived intravaginal ejaculatory latency time recording, Premature Ejaculation Diagnostic Tool score, and sexual frequency, attitudes, and behavior log. RESULTS: A total of 182 young patients with PE (age 31.2 ± 6.2 years) and 92 individuals without PE (age 30.7 ± 5.1 years) were included in the study. A total of 53.3% of patients with PE vs 17.4% of individuals without PE reported engaging in multiple sexual intercourse sessions within a single day in the past 4 weeks. PE patients who engaged in multiple intercourse sessions displayed better performance during the second attempt but performed poorly compared with individuals without PE. Scores for the first attempt in PE vs second attempt in individuals with PE vs without PE were the following: intravaginal ejaculatory latency time, 2.4 ± 1.6 vs 4.8 ± 5.7 vs 9.9 ± 9.4 (P < .001); Premature Ejaculation Diagnostic Tool, 14.9 ± 3.1 vs 12.7 ± 4.8 vs 5.2 ± 2.5 (P < .001); satisfaction, 2.9 ± 1.0 vs 3.1 ± 0.8 vs 3.7 ± 1.4 (P < .001). A total of 57.1% of patients held a negative attitude toward precoital masturbation, for reasons such as a reduced sexual desire (21.2%), the belief that masturbation is harmful (17.6%), concerns about erectile function (15.7%), fatigue (9.8%), and other mixed reasons (35.3%). CLINICAL IMPLICATIONS: Engaging in multiple intercourse sessions within a day is more common among the young PE population, and using precoital masturbation as a coping strategy is not universally applicable among patients with PE. STRENGTHS AND LIMITATIONS: This is the first study to explore symptom-coping strategies in patients with PE compared with individuals without PE. However, the conclusions cannot be generalized to the entire male population. CONCLUSION: Patients with PE, compared with individuals without PE, are more inclined to engage in multiple sexual intercourse sessions within a single sexual session, likely in an attempt to compensate for their first unsatisfactory sexual encounter. Moreover, the majority of patients with PE here studied hold a negative attitude toward using precoital masturbation as a coping strategy for symptoms.

Association between sickness presenteeism and depressive symptoms: a cross-sectional study using the 6th Korean working conditions survey.

PURPOSE: This study aimed to reveal the relationship of the days of experiencing sickness presentism and depressive symptoms among Korean workers. Sickness presenteeism which defined as the act of going to work despite being feeling unhealthy triggers various adverse effects on mental health, including increased risks of depression. Furthermore, Sickness presenteeism is a major social issue causing substantial socioeconomic costs. METHODS: The data of 25120 participants from sixth Korean Working Condition Survey was utilized in this cross-sectional study. Sickness presenteeism was defined using a self-reported questionnaire and depressive symptoms were assessed by WHO well-being index. Multivariate logistic regression analysis was conducted to calculate the odd ratios for depressive symptoms regarding the number of days experiencing sickness presenteeism. We calculated odds ratios (ORs) and 95% confidence interval (95% CI) for depressive symptoms after categorizing participants into three groups based on the duration of experiencing sickness presenteeism, using cut-off values of 3 and 5 days. RESULTS: Workers who have experienced sickness presenteeism for more than 5 days were at highest risk for depressive symptoms than referent group (OR 2.87; 95% CI 2.17-3.76 in male, OR 3.86; 95% CI 3.02-4.91 in female). Furthermore, there was a trend of increasing risk for depressive symptom as the duration of experiencing sickness presenteeism extended. CONCLUSION: This study presents the association between experiencing sickness presenteeism in the previous 12 months and depressive symptoms. Based on the results, we provide individual and organizational strategies of reducing sickness presenteeism. Also, screening for workers who have experienced sickness presenteeism are needed to ensure good mental health.

Art-based observational training for medical students and surgical residents in two Dutch museums.

Background: Art-based education is gaining interest in the medical field, particularly in specialties with a strong visual focus. Visual arts are increasingly used for the development of observational skills and social competencies. While content and objectives of art-based programs widely differ across medical faculties in the Netherlands, the diverse range of options underscore the interest in and the potential of this educational approach. In this report, we explore the value of art-based observational training for medical students and surgical residents in two prominent Dutch museums in Amsterdam and Rotterdam, respectively. Methods: Our program, conducted at the Rijksmuseum in Amsterdam and Depot Boijmans van Beuningen Museum in Rotterdam engaged medical students (n=24) and surgeons (in training) (n=66) in an interactive workshop focused on art observation led by an experienced art-educator and a clinical professional. Learning objectives were defined and a post-workshop questionnaire was devised to evaluate participants' perceptions, with a specific focus on contribution of the program to professional development. Results: Both residents and surgeons acknowledged that the program had a positive impact on their professional skills. The program learned them to postpone their judgements and contributed to the awareness of their personal bias. Notably, medical students believed in the program's potential contribution to their professional development. Surgeons were more critical in their evaluation, emphasizing the challenge of sustainable improvement of skills within the limited duration of the course. Conclusions: An interactive art-based medical education program was offered to medical students, PhD students, house officers, surgical residents and surgeons in two well known Dutch museums. Participants expressed enthusiasm for the innovative educational approach they experienced at the museums. They learned about the importance of critical observation in their professional work, handling of ambiguity and got the opportunity to practice both observational and communicational skills in a creative manner. The findings indicate that medical students and surgical residents can benefit from art-based observational training, using art as a vehicle to develop their professional competencies.

Exploring success factors and relationships in virtual learning using ISM and fuzzy MICMAC analysis.

The COVID-19 pandemic's consequences have led to a global change in educational settings towards online learning. The utilization of virtual learning (VL) has increased significantly. This study aimed to extract the success factors of VL and also examine the relationships among them. The research method involves examining factors identified in the literature review and seeking confirmation from experts using the Content Validity Index (CVI) method. Ten success factors are extracted and confirmed, including Technological, Management, Learning Capability, Pedagogical, Ethical, Resource Support, Interface Design, Evaluation, Institutional, and Study Environment. Based on the Interpretive Structural Model (ISM) method and the fuzzy matrix of cross-impact multiplications applied to classification (MICMAC), which divides the factors into five levels, the relationship between these factors is examined. Level I emphasizes the importance of evaluation mechanisms. Level II stresses integrating pedagogical, ethical, resource support, and institutional aspects. Level III highlights the alignment of learner capabilities with platform interfaces. Level IV underscores the significance of the learning environment. Lastly, Level V emphasizes the interplay between technology and management in VL's expansion. The findings of this study can be developed and customized through collaboration among instructors, learners, and institutions. Moreover, the findings from correlating success factors can be applied in practical learning experiments or utilized to develop efficient modeling manuals.

Sources of negative emotions and tactics of self-emotion regulation among college students during COVID-19 school closure in China.

Background: This study investigated the level of anxiety and depression in Chinese college students since the COVID-19 pandemic and explored the sources of their negative emotions and students' self-emotion regulation strategies. Methods: A stratified cluster sampling questionnaire was used to survey college students during the pandemic via the Anxiety Depression, Self-made Negative Emotion Source, and Negative Emotion Regulation Strategy Scales. Results: The prevalence of anxiety and depression was 23.3 and 20.1%, respectively. These levels were higher in women than in men. Furthermore, senior students reported higher levels than freshmen. Anxiety and depression mainly came from the pressure to grow and the narrowed scope of social activities. Proper relaxation via entertainment and communication with family and friends were popular ways of regulating their negative emotions. Conclusion: College students should confront their negative emotions and understand their source, use psychological methods to regulate their anxiety and depression or seek professional help, improve their psychological resilience, and adopt positive coping measures.

Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs. Recently, non-ADC delivery strategies for toxins have been extensively investigated. To further understand the application of toxins in anti-tumor, this paper provided an overview of prodrugs, nanodrug delivery systems, and biomimetic drug delivery systems. In addition, toxins and their combination strategies with other therapies were discussed. Finally, the prospect and challenge of toxins in cancer treatment were also summarized.

[The reversible share of cognitive deficits in older adults]. / La part réversible des déficits cognitifs chez les seniors.

Cognitive performance of older adults is very often inferior to that of younger adults on a variety of laboratory tests assessing basic functions such as memory, inhibition, or attention. Classic hypotheses and theories share the idea that these cognitive deficits are irreversible, due to profound cerebral changes. In this review article, we develop a more positive conception of aging, according to which cognitive deficits are not all irreversible, and can even be partially if not completely reversible. To this end, we present some of the most illustrative research on the reversibility of the effects of aging on cognition. We show how subtle contextual manipulations can change older adults' motivation and strategy, which improve their cognitive performance. We also show that guidance toward the selection of the most appropriate strategy, whether explicit as in selectivity paradigms or implicit as in dual-task procedures, can increase older adults' cognitive performance. We finally describe the hypotheses and theories that both account for low cognitive performance in old age and ways to reverse the effects of cognitive aging.

PET brain imaging in neurological disorders.

Brain disorders are a series of conditions with damage or loss of neurons, such as Parkinson's disease (PD), Alzheimer's disease (AD), or drug dependence. These individuals have gradual deterioration of cognitive, motor, and other central nervous system functions affected. This degenerative trajectory is intricately associated with dysregulations in neurotransmitter systems. Positron Emission Tomography (PET) imaging, employing radiopharmaceuticals and molecular imaging techniques, emerges as a crucial tool for detecting brain biomarkers. It offers invaluable insights for early diagnosis and distinguishing brain disorders. This article comprehensively reviews the application and progress of conventional and novel PET imaging agents in diagnosing brain disorders. Furthermore, it conducts a thorough analysis on merits and limitations. The article also provides a forward-looking perspective in the future development directions of PET imaging agents for diagnosing brain disorders and proposes potential innovative strategies. It aims to furnish clinicians and researchers with an all-encompassing overview of the latest advancements and forthcoming trends in the utilization of PET imaging for diagnosing brain disorders.